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Title: Association of the host immune response with protection using a live attenuated African swine fever virus model

Author
item CARLSON, JOLENE - Kansas State University
item O'DONNELL, VIVIAN - University Of Connecticut
item ALSFONSO, MARIALEXIA - Oak Ridge Institute For Science And Education (ORISE)
item VELAZQUEZ SALINAS, LAURO - Oak Ridge Institute For Science And Education (ORISE)
item Holinka-Patterson, Lauren
item Krug, Peter
item Gladue, Douglas
item HIGGS, STEPHEN - Kansas State University
item Borca, Manuel

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/16/2016
Publication Date: 10/22/2016
Citation: Carlson, J., O'Donnell, V., Alsfonso, M., Velazquez Salinas, L., Holinka-Patterson, L.G., Krug, P.W., Gladue, D.P., Higgs, S., Borca, M.V. 2016. Association of the host immune response with protection using a live attenuated african swine fever virus model. Viruses. 8(10):291. doi: 10.3390/v8100291.

Interpretive Summary: African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, African Swine Fever Virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to eliminate susceptible animals and restricted animal movement. Swine infected with experimental live attenuated strains are protected against challenge with a virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Here we use a model based in the use of the attenuated strain Pret4 delta 9GL virus. This animal model was used to associate the presence of host immune response and protection against the challenge. The presence of anti-ASFV antibodies, as well as ASFV-specific Interferon (IFN)-gamma interferon responses were assessed in different groups of animals that were challenged at different times post vaccination. Interestingly, the presence of ASFV-specific antibodies in the surviving swine associated with protection. On the contrary, no association was established between sensitization of cellular immunity and protection. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study where it is very plausible that protection against disease or infection relies heavily on the concurrence and or interaction of different host immune mechanisms.

Technical Abstract: African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, African Swine Fever Virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricted animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL ,Pret4 delta 9GL virus, is completely attenuated. Swine infected with Pret4 delta 9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 dpi showed a progressive acquisition of protection, from 40% at 7dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response and protection against the challenge. The presence of anti-ASFV antibodies, as well as ASFV-specific interferon (IFN)-gamma production in primary blood macrophage cells (PBMCs), and cytokines in serum were assessed in each group. Interestingly, with the exception of ASFV-specific antibodies in the surviving swine challenged at 21 and 28 dpi, no solid association between any of the parameters assessed and the extent of protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study where it is very plausible that protection against disease or infection relies heavily on the concurrence and or interaction of different host immune mechanisms.